Algorithm Validation for Quantifying ActiGraph™ Physical Activity Metrics in Individuals with Chronic Low Back Pain and Healthy Controls.

Assessing physical activity is important in the treatment of chronic conditions, including chronic low back pain (cLBP). ActiGraph™, a widely used physical activity monitor, collects raw acceleration data, and processes these data through proprietary algorithms to produce physical activity measures. The purpose of this study was to replicate ActiGraph™ algorithms in MATLAB and test the validity of this method with both healthy controls and participants with cLBP. MATLAB code was developed to replicate ActiGraph™'s activity counts and step counts algorithms, to sum the activity counts into counts per minute (CPM), and categorize each minute into activity intensity cut points. A free-living validation was performed where 24 individuals, 12 cLBP and 12 healthy, wore an ActiGraph™ GT9X on their non-dominant hip for up to seven days. The raw acceleration data were processed in both ActiLife™ (v6), ActiGraph™'s data analysis software platform, and through MATLAB (2022a). Percent errors between methods for all 24 participants, as well as separated by cLBP and healthy, were all less than 2%. ActiGraph™ algorithms were replicated and validated for both populations, based on minimal error differences between ActiLife™ and MATLAB, allowing researchers to analyze data from any accelerometer in a manner comparable to ActiLife™.

Effects of Sedentary Behavior Reduction on Blood Pressure in Desk Workers: Results From the RESET-BP Randomized Clinical Trial.

BACKGROUND: Sedentary behavior (SB) is observationally associated with cardiovascular disease risk. However, randomized clinical trials testing causation are limited. We hypothesized that reducing SB would decrease blood pressure (BP) and pulse wave velocity (PWV) in sedentary adults. METHODS: This parallel-arm, 3-month randomized clinical trial recruited desk workers, age 18 to 65 years, with systolic BP 120 to 159 or diastolic BP (DBP) 80 to 99 mm Hg, off antihypertensive medications, and reporting <150 min/wk of moderate to vigorous intensity physical activity. Participants were randomized to a SB reduction intervention or a no-contact control group. The intervention sought to replace 2 to 4 h/d of SB with standing and stepping through coaching, a wrist-worn activity prompter, and a sit-stand desk. SB and physical activity were measured with a thigh-worn accelerometer and quantified during all waking hours and separately during work and nonwork times. Clinic-based resting systolic BP (primary outcome) and DBP, 24-hour ambulatory BP, and PWV were assessed by blinded technicians at baseline and 3 months. RESULTS: Participants (n=271) had a mean age of 45 years and systolic BP/DBP 129/83 mm Hg. Compared with controls, intervention participants had reduced SB (-1.15±0.17 h/d), increased standing (0.94±0.14 h/d), and increased stepping (5.4±2.4 min/d; all P<0.05). SB and activity changes mainly occurred during work time and were below the goal. The intervention did not reduce BP or PWV in the intervention group compared with controls. Between-group differences in resting systolic BP and DBP changes were -0.22±0.90 (P=0.808) and 0.13±0.61 mm Hg (P=0.827), respectively. The findings were similarly null for ambulatory BP and PWV. Decreases in work-time SB were associated with favorable reductions in resting DBP (r=0.15, P=0.017). Contrary to our hypotheses, reductions in work-time SB (r=-0.19, P=0.006) and increases in work-time standing (r=0.17, P=0.011) were associated with unfavorable increases in carotid-femoral PWV. As expected, increases in non-work-time standing were favorably associated with carotid-femoral PWV (r=-0.14, P=0.038). CONCLUSIONS: A 3-month intervention that decreased SB and increased standing by ≈1 hour during the work day was not effective for reducing BP. Future directions include examining effects of interventions reducing SB through activity other than work-time standing and clarifying association between standing and PWV in opposite directions for work and nonwork time. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03307343.

Non-exercise estimated cardiorespiratory fitness and incident type 2 diabetes in adults.

AIM(S): To examine the association between non-exercise estimated cardiorespiratory fitness (eCRF) and incident type 2 diabetes. METHODS: In a sample of 13,616 men and women without diabetes at baseline, incident type 2 diabetes were determined as fasting plasma glucose level ≥ 7 mmol/l (126 mg/dL), self-report, or insulin usage at follow-up. eCRF was calculated in metabolic equivalents (METs) at baseline using sex-specific algorithms, including physical activity, smoking status, age, body mass index, waist circumference, and resting heart rate. Cox regression models were performed, and hazard ratios (HRs), 95 % confidence intervals (CIs), and p values were reported. RESULTS: Each 1-MET unit increase in eCRF was associated with an 11 % lower risk of incident type 2 diabetes (p < 0.0001). Men in the upper and middle eCRF tertiles were at 46 % (95 % CI, 0.42-0.68) and 29 % (95 % CI, 0.57-0.88) lower risk of incident type 2 diabetes compared to the lower eCRF tertile (p < 0.0001). For women, there were no significant findings between eCRF tertiles and incident type 2 diabetes (p ≥ 0.11 for all). CONCLUSIONS: Higher eCRF was associated with a lower incidence of type 2 diabetes in men. Further research needs to examine the association between eCRF and type 2 diabetes in women.

Impact of a digital employer-based weight loss program on individuals age 65 or older.

Introduction: Older adults are not protected from obesity, which has been linked to frailty, cognitive impairment, and other aging-related factors. Intensive lifestyle interventions have been shown to be effective for weight loss in older adults; however, these have typically been highly intensive and less feasible for dissemination. This analysis describes weight loss in a large-scale, commercially available, digital intervention in a subset of older adults. Methods: Older adults (N = 20,443, males = 6,238; females = 14,205) between 65 and 85 years of age with overweight (43.3%) or obesity (46.7%) participated in an online, self-directed weight loss program. Behavioral-based content was delivered through weekly video lessons within an online platform that included weight and physical activity tracking, an online community, a reference library, and access to coaching support. Self-reported measures taken at the time of entry into the program were used for this analysis (demographics, height, body weight, and health status). Weight was reported across weeks of engagement in the curriculum. Results: The average weight loss was -3.15 kg (95% CI: [-3.20, -3.11]) at 15.5 weeks. Weight loss was significantly greater in male individuals (-3.79 kg [95% CI: -3.89, -3.71]) versus female individuals (-2.87 kg [95% CI: -2.94, -2.82]) (p < 0.001), with a similar engagement in curriculum weeks. Percent weight loss was statistically significant for all age categories (p < 0.05) and self-reported health conditions (p < 0.05). Discussion: Short-term weight loss was observed in older adults exposed to a low-touch, self-guided, and digital behavioral-based weight loss program. Weight loss was also observed even in the presence of various chronic health conditions.

Predicting physical activity by the personality styles of the five-factor model.

OBJECTIVE: Low neuroticism, high extraversion, and high conscientiousness are related to physical activity (PA). We tested whether the small size and heterogeneity of these relationships result because personality traits influence one another as well as because some narrow facets rather than the broad domains contain more specific variance relevant to PA. METHOD: Participants were men and women enrolled in the University of North Carolina Alumni Heart Study who completed the Revised NEO Personality Inventory (NEO-PI-R) and reported their past month's average activity on an 8-point scale. In Study 1, we examined prospective correlations between the five NEO-PI-R domains and PA. In Studies 2 and 3, we used multinomial logistic regression to examine associations between PA and trait pair combinations (personality styles) controlling for age, sex, educational achievement, relationship status, and depression. RESULTS: Study 1 revealed that lower neuroticism (N) and agreeableness (A) and higher conscientiousness (C) predicted more PA. Taken together, Studies 2 and 3 found that the combination of high Extraversion (E) and high openness (O) was related to higher PA and that combinations of low E and high A and low E and low C were related to lower PA. Study 3, which examined the activity facet of E (E4), found that E4 is an important driver of E-PA associations. CONCLUSIONS: Personality traits do not operate in isolation. They may influence how other traits are expressed and such nonadditive effects can impact PA. Assessment of personality styles could help to identify individuals at risk for PA avoidance and may be useful for developing personalized interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a preclinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 wk of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 wk. The adult component also includes recruitment of highly active endurance-trained or resistance-trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.NEW & NOTEWORTHY The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will be the first large trial to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. By generating a compendium of the molecular responses to exercise, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. Presented here is the design, protocols, and procedures for the MoTrPAC human studies.

Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes.

Importance: Randomized clinical trials of bariatric surgery have been limited in size, type of surgical procedure, and follow-up duration. Objective: To determine long-term glycemic control and safety of bariatric surgery compared with medical/lifestyle management of type 2 diabetes. Design, Setting, and Participants: ARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) is a pooled analysis from 4 US single-center randomized trials conducted between May 2007 and August 2013, with observational follow-up through July 2022. Intervention: Participants were originally randomized to undergo either medical/lifestyle management or 1 of the following 3 bariatric surgical procedures: Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding. Main Outcome and Measures: The primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 7 years for all participants. Data are reported for up to 12 years. Results: A total of 262 of 305 eligible participants (86%) enrolled in long-term follow-up for this pooled analysis. The mean (SD) age of participants was 49.9 (8.3) years, mean (SD) body mass index was 36.4 (3.5), 68.3% were women, 31% were Black, and 67.2% were White. During follow-up, 25% of participants randomized to undergo medical/lifestyle management underwent bariatric surgery. The median follow-up was 11 years. At 7 years, HbA1c decreased by 0.2% (95% CI, -0.5% to 0.2%), from a baseline of 8.2%, in the medical/lifestyle group and by 1.6% (95% CI, -1.8% to -1.3%), from a baseline of 8.7%, in the bariatric surgery group. The between-group difference was -1.4% (95% CI, -1.8% to -1.0%; P < .001) at 7 years and -1.1% (95% CI, -1.7% to -0.5%; P = .002) at 12 years. Fewer antidiabetes medications were used in the bariatric surgery group. Diabetes remission was greater after bariatric surgery (6.2% in the medical/lifestyle group vs 18.2% in the bariatric surgery group; P = .02) at 7 years and at 12 years (0.0% in the medical/lifestyle group vs 12.7% in the bariatric surgery group; P < .001). There were 4 deaths (2.2%), 2 in each group, and no differences in major cardiovascular adverse events. Anemia, fractures, and gastrointestinal adverse events were more common after bariatric surgery. Conclusion and Relevance: After 7 to 12 years of follow-up, individuals originally randomized to undergo bariatric surgery compared with medical/lifestyle intervention had superior glycemic control with less diabetes medication use and higher rates of diabetes remission. Trial Registration: ClinicalTrials.gov Identifier: NCT02328599.

Accumulated physical activity and the association with obesity, fitness, and cardiometabolic risk factors in healthy adults.

OBJECTIVE: This study examined the prevalence of ≥150 min/wk of moderate-to-vigorous physical activity (MVPA) using different criteria for bout length and to examine associations with measures of obesity, cardiorespiratory fitness, and cardiometabolic risk factors in healthy adults with overweight or obesity. METHODS: Baseline data from healthy adults (N = 375; age [mean ± SD] = 45.2 ± 7.7 years; BMI = 32.3 ± 3.8 kg/m2 ) enrolled in a behavioral weight-loss intervention were examined cross-sectionally. Categorization was by objectively measured MVPA as follows: 1) LOW-MVPA: <150 min/wk (n = 122, 32.5%); 2) MVPA-NON-BOUTED: ≥150 min/wk in bouts < 10 min (n = 72, 19.2%); 3) MVPA-COMBINED: ≥150 min/wk with a combination of bouts < 10 and ≥10 min (n = 50, 13.3%); and 4) MVPA-BOUTED: ≥150 min/wk with bouts ≥ 10 min (n = 131, 34.9%). RESULTS: Weight, BMI, and waist circumference were higher in the LOW-MVPA category versus the other categories. Body fatness was significantly lower in the MVPA-BOUTED category compared with the LOW-MVPA category (p < 0.05). Differences by category for cardiorespiratory fitness and cardiometabolic risk factors were limited. CONCLUSIONS: Some adults with overweight or obesity may be more active than they perceived themselves to be, and accumulation of ≥150 min/wk of MVPA may have favorable effects on weight and adiposity status. Findings may influence physical activity recommendations, and confirmation with prospective and randomized studies is needed.

Physical activity in the new era of antiobesity medications.

Contemporary antiobesity medications (AOMs) are highly efficacious for the treatment of obesity and obesity-related comorbidities. Given this effectiveness, lifestyle factors within the context of AOM treatments need to refocus and move away from efforts to enhance weight loss. Rather, lifestyle considerations should pivot to being complementary to the benefits realized with AOM treatment and be redirected to enhancing holistic patient health and well-being. Physical activity is an important lifestyle behavior that contributes to many health benefits both in conjunction with, and in the absence of, weight loss. Physical activity improves cardiorespiratory fitness, muscle strength, and physical function. Physical activity may attenuate the loss of lean mass that is observed with AOM treatments and may enhance the quality and function of muscle. Physical activity is a key behavior for holistic health within this era of contemporary AOMs that warrants appropriate attention within the clinical care of patients.

The Role of Lifestyle Modification with Second-Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities.

PURPOSE OF REVIEW: This review examines lifestyle modification for obesity management with the goal of identifying treatment components that could support the use of a new generation of anti-obesity medications (AOMs). RECENT FINDINGS: Semaglutide reliably reduces baseline body weight by approximately 15% at 68 weeks, in contrast to 5-10% for lifestyle modification. Tirzepatide induces mean losses as great as 20.9%. Both medications reduce energy intake by markedly enhancing satiation and decreasing hunger, and they appear to lessen the need for traditional cognitive and behavioral strategies (e.g., monitoring food intake) to achieve calorie restriction. Little, however, is known about whether patients who lose weight with these AOMs adopt healthy diet and activity patterns needed to optimize body composition, cardiometabolic health, and quality of life. When used with the new AOMs, the focus of lifestyle modification is likely to change from inducing weight loss (through calorie restriction) to facilitating patients' adoption of dietary and activity patterns that will promote optimal changes in body composition and overall health.

Demographic, Clinical, and Psychosocial Predictors of Exercise Adherence: The STRRIDE Trials.

Purpose: To identify baseline demographic, clinical, and psychosocial predictors of exercise intervention adherence in the Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trials. Methods: A total of 947 adults with dyslipidemia or prediabetes were enrolled into an inactive control group or one of ten exercise interventions with doses of 10-23 kcal/kg/week, intensities of 40-80% of peak oxygen consumption, and training for 6-8-months. Two groups included resistance training. Mean percent aerobic and resistance adherence were calculated as the amount completed divided by the prescribed weekly minutes or total sets of exercise times 100, respectively. Thirty-eight clinical, demographic, and psychosocial measures were considered for three separate models: 1) clinical + demographic factors, 2) psychosocial factors, and 3) all measures. A backward bootstrapped variable selection algorithm and multiple regressions were performed for each model. Results: In the clinical and demographic measures model (n=947), variables explained 16.7% of the variance in adherence (p<0.001); lesser fasting glucose explained the greatest amount of variance (partial R2 = 3.2%). In the psychosocial factors model (n=561), variables explained 19.3% of the variance in adherence (p<0.001); greater 36-Item Short Form Health Survey (SF-36) physical component score explained the greatest amount of variance (partial R2 = 8.7%). In the model with all clinical, demographic, and psychosocial measures (n=561), variables explained 22.1% of the variance (p<0.001); greater SF-36 physical component score explained the greatest amount of variance (partial R2 = 8.9%). SF-36 physical component score was the only variable to account for >5% of the variance in adherence in any of the models. Conclusions: Baseline demographic, clinical, and psychosocial variables explain approximately 22% of the variance in exercise adherence. The limited variance explained suggests future research should investigate additional measures to better identify participants who are at risk for poor exercise intervention adherence.

Association of Eating Behaviors with Variability in Weight Change in Response to Physical Activity Interventions in Adults with Overweight.

There is individual variability in weight change in response to physical activity interventions. Secondary analyses explored whether there were differences in physical activity, dietary intake, and the domains of hunger, dietary disinhibition, or dietary restraint in response to different physical activity interventions and by pattern of weight change across 6 months of an intervention. Participants (N = 207; age: 44.8 ± 8.2 years; body mass index: 27.0 ± 1.7 kg/m2) were included in these secondary analyses. Participants were randomly assigned to (1) a self-help physical activity intervention, (2) a prescription to progress to 150 min/week of physical activity, or (3) a prescription to progress to 300 min/week of physical activity and following 6 months were categorized based on weight change (weight gain, stability, or loss). Intervention conditions did not differ for change in weight, physical activity, dietary intake, and measures of hunger, dietary disinhibition, and total dietary restraint. Categories of weight change did not differ for change in physical activity or dietary intake, but the category of weight loss had significantly greater decreases in hunger and increases in flexible dietary restraint compared to the categories of weight stability and weight gain. The findings may provide insight into the variability in weight change in response to physical activity.

Physical Activity for Health-Every Minute Counts.

This Viewpoint discusses the amount of physical activity recommended by the Physical Activity Guidelines for Americans, 2nd Edition, and how clinicians should use these recommendations to personalize and set achievable physical activity goals for their patients.

Use of a Mobile-Assisted Telehealth Regimen to Increase Exercise in Transplant Candidates: A Home-Based Prehabilitation Pilot and Feasibility Trial.

INTRODUCTION: Physical fitness assessed by the Liver Frailty Index (LFI) and 6-minute walk test (6MWT) informs the prognosis of liver transplant candidates, although there are limited data on its reversibility after prehabilitation. On a home-based exercise trial, we aimed to improve LFI and 6MWT and to investigate trial feasibility and intervention adherence. METHODS: Liver transplant candidates with cirrhosis wore a personal activity tracker and used Exercise and Liver FITness app for 14 weeks, including a 2-week technology acclimation run-in. The 12-week intervention consisted of Exercise and Liver FITness app plus personal activity tracker and 15-/30-minute weekly calls with a physical activity coach aiming to complete ≥2 video-training sessions/week, or ≥500 step/d baseline increase for ≥8 weeks. We defined feasibility as ≥66% of subjects engaging in the intervention phase and adherence as ≥50% subjects meeting training end point. RESULTS: Thirty-one patients (61 ± 7 years, 71% female, model for end-stage liver disease 17 ± 5, ∼33% frail) consented and 21 (68%) started the intervention. In the 15 subjects who completed the study, LFI improved from 3.84 ± 0.71 to 3.47 ± 0.90 ( P = 0.03) and 6MWT from 318 ± 73 to 358 ± 64 m ( P = 0.005). Attrition reasons included death (n = 4) and surgery (n = 2). There was 57% adherence, better for videos than for walking, although daily steps significantly increased (3,508 vs baseline: 1,260) during best performance week. One adverse event was attributed to the intervention. DISCUSSION: Our clinical trial meaningfully improved LFI by 0.4 and 6MWT by 41 m and met feasibility/adherence goals. In-training daily step increase supported physical self-efficacy and intervention uptake, but maintenance remained a challenge despite counseling.

Race and sex differences in dropout from the STRRIDE trials.

Purpose: To determine if race and sex differences exist in determinants and timing of dropout among individuals enrolled in an exercise and/or caloric restriction intervention. Methods: A total of 947 adults with dyslipidemia (STRRIDE I, STRRIDE AT/RT) or prediabetes (STRRIDE-PD) were randomized to either inactive control or to 1 of 10 exercise interventions, ranging from doses of 8-23 kcal/kg/week, intensities of 50%-75% V˙O2 peak, and durations of 6-8 months. Two groups included resistance training, and one included a dietary intervention (7% weight loss goal). Dropout was defined as an individual withdrawn from the study, with the reasons for dropout aggregated into determinant categories. Timing of dropout was defined as the last session attended and aggregated into phases (i.e., "ramp" period to allow gradual adaptation to exercise prescription). Utilizing descriptive statistics, percentages were generated according to categories of determinants and timing of dropout to describe the proportion of individuals who fell within each category. Results: Black men and women were more likely to be lost to follow-up (Black men: 31.3% and Black women: 19.6%), or dropout due to work responsibilities (15.6% and 12.5%), "change of mind" (12.5% and 8.9%), transportation issues (6.3% and 3.6%), or reported lack of motivation (6.3% and 3.6%). Women in general noted lack of time more often than men as a reason for dropout (White women: 22.4% and Black women: 22.1%). Regardless of race and sex, most participants dropped out during the ramp period of the exercise intervention; with Black women (50%) and White men (37.1%) having the highest dropout rate during this period. Conclusion: These findings emphasize the importance of targeted retention strategies when aiming to address race and sex differences that exist in determinants and timing of dropout among individuals enrolled in an exercise and/or caloric restriction intervention.

Change in circulating klotho in response to weight loss, with and without exercise, in adults with overweight or obesity.

Introduction: Klotho is a protein associated with protection from aging-related diseases and health conditions. Obesity is associated with lower Klotho concentrations. Thus, this secondary analysis of adults with obesity examined 1) the change in serum Klotho concentration in response to a behavioral weight loss intervention by the magnitude of weight loss achieved; and 2) the association among serum Klotho concentration and weight, body composition, and cardiorespiratory fitness. Methods: Participants were randomized to either diet alone (DIET), diet plus 150 min of physical activity per week (DIET + PA150), or diet plus 250 min of physical activity per week (DIET + PA250). Participants [n = 152; age: 45.0 ± 7.9 years; body mass index (BMI): 32.4 ± 3.8 kg/m2] included in this secondary analysis provided blood samples at baseline, 6-, and 12 months, and were classified by weight loss response (Responder: achieved ≥10% weight loss at 6 or 12 months; Non-responder: achieved <5% weight loss at both 6 and 12 months). Serum Klotho was measured using a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). Analyses of covariance (ANCOVA's) were used to examine changes in weight, body composition, cardiorespiratory fitness, and Klotho concentration by weight loss response across the 12-month weight loss intervention. Results: Responders had a greater reduction in measures of weight and body composition, and a greater increase in cardiorespiratory fitness, compared to Non-Responders (p < 0.05). Change in Klotho concentration differed between Responders and Non-Responders (p < 0.05), with the increase in Klotho concentration from baseline to 6 months for Responders being statistically significant. The 6-month change in Klotho concentration was inversely associated with the 6-month change in weight (r s = -0.195), BMI (r s = -0.196), fat mass (r s = -0.184), and waist circumference (r s = -0.218) (p-values <0.05). Discussion: Findings provide evidence within the context of a behavioral intervention, with and without exercise, that change in Klotho concentration is significantly different between adults with weight loss ≥10% compared to <5% across 12 months. These findings suggest that weight loss and reduction in fat mass may be favorably associated with the change in Klotho concentration. This may reduce the risk of negative health consequences associated with accelerated aging in middle-aged adults.

Exercise-primed extracellular vesicles improve cell-matrix adhesion and chondrocyte health.

Extracellular vesicles (EVs) have been suggested to transmit the health-promoting effects of exercise throughout the body. Yet, the mechanisms by which beneficial information is transmitted from extracellular vesicles to recipient cells are poorly understood, precluding a holistic understanding of how exercise promotes cellular and tissue health. In this study, using articular cartilage as a model, we introduced a network medicine paradigm to simulate how exercise facilitates communication between circulating EVs and chondrocytes, the cells resident in articular cartilage. Using the archived small RNA-seq data of EV before and after aerobic exercise, microRNA regulatory network analysis based on network propagation inferred that circulating EVs activated by aerobic exercise perturb chondrocyte-matrix interactions and downstream cellular aging processes. Building on the mechanistic framework identified through computational analyses, follow up experimental studies interrogated the direct influence of exercise on EV-mediated chondrocyte-matrix interactions. We found that pathogenic matrix signaling in chondrocytes was abrogated in the presence of exercise-primed EVs, restoring a more youthful phenotype, as determined by chondrocyte morphological profiling and evaluation of chondrogenicity. Epigenetic reprograming of the gene encoding the longevity protein, α-Klotho, mediated these effects. These studies provide mechanistic evidence that exercise transduces rejuvenation signals to circulating EVs, endowing EVs with the capacity to ameliorate cellular health even in the presence of an unfavorable microenvironmental signals.

Long-term effects of an internalized weight stigma intervention: A randomized controlled trial.

OBJECTIVE: To test the long-term effects of a group-based, psychological intervention designed to reduce internalized weight stigma (IWS, i.e., self-stigma), delivered in combination with behavioral weight loss (BWL) treatment, compared to BWL alone. METHOD: Adults with obesity who had experienced and IWS (N = 105, Mage = 49 years, 90.5% women, 70.5% White, 24.8% Black, MBMI = 38 kg/m²) were randomized to receive BWL with the Weight Bias Internalization and Stigma (BIAS) Program or BWL alone. Participants received weekly group treatment for 20 weeks, followed by 52 weeks of monthly and every-other-month sessions. Percent weight change at Week 72 was the primary outcome, with secondary outcomes of weight change at other time points; physical activity (measured by accelerometry, interview, and self-report); cardiometabolic risk factors; and psychological and behavioral outcomes. Intention-to-treat analyses used linear mixed models to test for between-group differences. Treatment acceptability was assessed. RESULTS: Participants in the BWL + BIAS versus BWL group lost 2 percentage points more of baseline weight at Week 72, which was not a significant difference (mean weight change = -7.2% vs. -5.2%, 95% CI [-4.6 to 0.6], p = 0.14, d = 0.18). The BWL + BIAS (vs. BWL) group produced significantly greater improvements in weight self-stigma, eating self-efficacy, and some aspects of quality of life at specific time points. Most outcomes improved significantly over time but did not differ between groups. The trial had high retention and treatment acceptability, with higher ratings in the BWL + BIAS versus BWL group. CONCLUSIONS: No significant differences in weight loss were observed between the BWL + BIAS versus BWL group. Possible benefits of addressing weight stigma in weight management warrant further investigation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).